School of Veterinary Medicine University of Pennsylvania Philadelphia, PA 19104-6010

CATS THAT DO NOT use their litter boxes are often relinquished to shelters or euthanatized. A thorough history will generally reveal a pattern of elimination involving a specific diagnosis. Treatment directed at resolving the diagnosed problem has environmental, behavioral, and pharmacologic components. When all three of these components are addressed, problems usually resolve.

An overall plan for outlining the behavior and environmental modifications for elimination disorders associated with aggression is found in Table 1. A history questionnaire is found in Table 2. An outline of the steps for the treatment of these conditions is found in Table 3. Specific dosages of drugs used to treat feline aggression and elimination disorders associated with feline aggression are found in Table 4.

Steps to determine what will work for each cat To treat feline elimination disorders, follow the same steps used for treating any other behavior problem. First, rule out or treat any underlying medical cause of the problem. While not generally implicated as a primary cause of problem elimination in cats, any potential underlying medical problem must be addressed.1 Medical problems that can be associated with problem elimination behavior or may complicate its treatment include gastrointestinal disease, endoparasites, bacterial disease, inflammatory disease, anatomical abnormalities, partial or complete obstructions, nutritional disorders such as maldigestion and malabsorption syndromes, metabolic disease, food allergies, or debilitating conditions that preclude easy access to appropriate elimination areas, such as arthritis. Only after other potential causes have been ruled out should you proceed with the premise that an elimination disorder is rooted in behavior. Generally, this step can be quickly and effectively completed.

The second step to treating any marking situation or substrate or location aversion or preference is to remove the odor. All affected areas and layers must be cleaned with a good odor eliminator. This means that, for example, the wall-to-wall carpeting, pad underneath it, and subfloor all need to be cleaned or replaced. If this is not possible, the client can seal the connecting areas with either physical moisture barriers (e.g. heavy plastic) or chemical moisture barriers (e.g. epoxy paints) that can be painted on the subfloor. In some cases, floorboards or tiles will need to be replaced. Odor eliminators that have been relatively successful include The Equalizer T11 (EVSCO), K.O.E.- (Kennel Odor Eliminator) (Thornell), Elimin-odors (Pfizer), and Anti-Icky Pool (AIP) (Bug-a-Boo Chemical). No odor eliminator can be expected to undo years of repeated assaults. Accordingly, clients need to be told of the importance of early treatment for elimination disorders the same way they are educated about prophylactic vaccinations. Behavior problems appear to kill more cats annually than does viral disease.

After they are cleaned, affected areas should be covered with heavy plastic to change the tactile sensation for the cat and to prevent penetration in the event of further elimination. While floors are being cleaned and sealed, it would be preferable to isolate the cat to an area where controlled tests with litter boxes and different substrates can be conducted. It is critical that the cat can no longer smell where it has been eliminating.

Encourage the client to provide multiple litter boxes, generally one more than there are cats, unless the clients are inundated with cats. Large numbers of cats may make it impossible to prevent the cats from responding to olfactory stimuli. In households with 10 or more cats, there is virtually a 100% probability that one of those cats will spray at least once.2,3 While this does not guarantee that the frequency of spraying will increase with an increasing number of cats or decrease if a cat leaves, it reemphasizes the importance of the social system in the hierarchy. Because litter boxes can be implicated as turf in social conflicts, it is critical to allot the litter box turf in a manner that will convince the cats to use the boxes appropriately. Litter boxes should be placed in several locations and should be offered in a variety o1 styles (open, covered, deep, shallow, big, small). Data from the Veterinary Hospital of the University of Pennsylvania 1993 feline questionnaires indicate that the instantaneous use of a clean litter box can be related to hierarchy, in that the highest-ranking cat uses it first. This is also supported by studies of house cats.4

Litter needs to be scooped every day, and most litter should be dumped every other day. This is good advice for owners of cats without elimination problems, too, because the cats may be tolerating a litter without liking it. It is unknown if such behavior is a risk factor for developing future elimination problems. Exceptions are with the clumping litters and the litter boxes that have stones and pads that absorb moisture. In the latter case, the pad is discarded daily and the stones are washed weekly. With the clumping litters, the soiled litter clumps can be easily removed while the remaining litter is relatively uncontaminated. Clumping litters need to be dumped every week to every few weeks. Without exception, boxes should be washed weekly. Boxes that are so permeated with sand or scratched that cleaning will not eliminate odor should be discarded.

A variety of litters should be offered in a variety of boxes. Use litters that resemble the inappropriate substances the cat has chosen to use. If the cat is using soft substrates such as bedding, towels, or laundry, consider softer litters. No. 3 blasting sand and fine-grade playground sand are inexpensive and soft to the touch. They do not absorb moisture or odor as well as some commercial litters, but they can be dumped multiple times a day at very little expense. Shredded newspaper or paper towels are also relatively inexpensive and soft but do not absorb moisture or scent as well as traditional litters. Yesterday's News® (Canbrands International) is a litter made from recycled newspapers that is formulated to absorb moisture well but is not as good at absorbing odors as some other litters. Many cats that are very fussy about using soft substrates will use this litter in the absence of any others.

Sawdust or wood chips that do not originate from strong-smelling trees (e.g. cedar) can be useful additives in litter boxes. Saw mills may allow clients to have these for free or for a very small charge. Some of the newer clay litters have pine chips added to provide softening. The most successful results appear to be obtained by using recyclable, clumping litters.5 Clients need to be observant and creative to determine which litter is preferred.

If the problem involves a location preference or aversion, a litter box with a litter that the cat likes can be placed where the cat is eliminating. If the cat starts to use the box, you know you are dealing with a location preference or aversion. If the cat does not use it, the client must go through the sampling procedure outlined here.

Counterconditioning can work for some disorders involving locations. Food dishes can be placed in the affected area. Generally, cats will not eliminate where they are fed. If there are several inappropriate locations, this will not work, but if this is the case a location preference is probably not the problem. Clients can rearrange furniture or move a large plant so that the cat's favorite spot is covered. Sometimes the cat then shifts its spot. This can indicate that the location wasn't sufficiently altered, or it can suggest a mixed substrate-location preference.

A cat with an elimination problem can be encouraged to make positive associations with the litter box. This can be done by taking the cat to the litter box frequently and waiting with the cat. If it uses the box, it should be praised. Associate the appropriate elimination behaviors, such as scratching in the box, with giving the cat a food treat or anything that encourages the cat to use its litter box. Cats should not be disturbed or frightened while they are in the litter box.

Owners will learn to recognize behaviors that precede elimination, such as facial expressions in some cats. If the cat is seen squatting outside the box, the owner should startle the cat so that it stops the inappropriate behavior and place it in a situation where an appropriate behavior can be encouraged. If startled within the first 30 to 60 seconds of the complete behavioral sequence (sniffing, turning, and scratching), the cat will be able to learn from the startle. If the cat has already eliminated and is digging, it is fruitless to startle or correct the cat. Psychologists have demonstrated that individuals learn best if they are interrupted in the act of an inappropriate behavior. The interruption must come within the first few seconds of but no later than 30 to 60 seconds after the onset of the inappropriate behavior. If the cat is startled after it has eliminated and while it is digging in the carpet, the cat may be taught only to become more secretive or to abort the last phase of the elimination behavior. The startle must be sufficient to make the cat abort the behavior and leave but cannot be so horrific that the cat becomes fearful, so the startling technique needed will vary from cat to cat. Appropriate initial startles include soft noises such as a hiss or handclap.

Placing a bell on the cat's collar can help an owner who is trying to observe the cat's elimination behavior. The preferred collar type is a feline breakaway collar. Because cats are prone to squeeze themselves through strange spaces, even regular, flat buckle collars can be dangerous. Any cat that wears a collar should wear a breakaway collar.

If the problem has been occurring for a long time, it is best to separate the cat from the other cats in the household. The confined cat needs the same amount of attention (grooming, play) it would have received had it not been confined. The cat should be placed in a room that has not been previously soiled and should be offered food, water, and a choice of litters and litter box styles.

A problem in the social hierarchy in the household will influence where the cat is incarcerated. High-ranking animals can displace others at feeding, sleeping, and elimination sites without resorting to overt aggression or threats. Others defer to them and relinquish space. High-ranking individuals generally are groomed by lower-ranking individuals. Sometimes, low-ranking animals readily relinquish space to high-ranking cats but may continue to be bullied by them. The higher-ranking cat will continue to force the cat into smaller, less desirable areas of the house in ways that are not always obvious. Clients usually notice that something is different in the interactions when one cat no longer emerges from a corner of the basement. Cats can also be of relatively equal status or not care about status; such cats will groom each other and share toys, beds, sunning spots, and food.

If a high-ranking cat is being medicated for spraying (discussed below), it is critical that it be isolated while adjusting to therapeutic drug levels. It is inappropriate to isolate the aggressor in an area of the home that it prefers (e.g. kitchens, bedrooms, rooms with picture windows commonly used as perch sites). The aggressor must accept that other animals are allowed to live in the household, and one way the owner can passively reinforce that is to put the aggressor in a neutral (e.g. rooms occasionally used) or lower-quality (e.g. rooms rarely used) room. In this context, lower quality is determined by social attributes, such as access to perches, windows, and human presence, not physical attributes. Thus, high-quality rooms would include those often used (e.g. kitchen, bedroom). Appropriate rooms for this isolation are safe and comfortable but not among the cat's preferred areas. It would be inappropriate to enclose the animal in a damp garage or basement. Cats should always have perch sites.

If the cat with the elimination problem is a lower-ranking animal and you suspect that part of the problem is due to its inability to assert itself in the social hierarchy, it is best to isolate that animal in an area of high status. If the cats sleep with the client, the place to keep the problem cat all day is in the bedroom. The cat does not know where the other cats are, but they will be able to tell that this animal has been allowed to occupy the high-quality area.

When there are two equally matched aggressive animals, it is best to either separate them into neutral areas or to alternate between the high-quality and neutral or low-quality areas. Regardless, it is critical to monitor their elimination behaviors while they are in these rooms, because if they start to spray or continue not to use the litter box, it is important that additional substrates not be soiled. Once the animals are using the appropriate substrate for elimination, they can be released from the confined area gradually. This means that they are to be belled, again with a breakaway collar, and for increasing periods of time over a few weeks gradually reintroduced to small sections of the house only when supervised. If after a few weeks the clients have not had problems with other cats in the household or with elimination in any other area, they can increase the amount of time that the cat is allowed to be free over the next week until the cat again has free range.

TABLE I

Behavior and Environmental Modification for Elimination Disorders Associated with Aggression

1. Reduce stressors and anxiety-provoking events.

a. Separate animals when they are unsupervised.

b. Provide additional turf (eg, empty boxes, kitty condos).

c. Cover windows.

d. In cases of any aggression associated with status or active aggression, banish the aggressor to less desirable turf.

2. Use counterconditioning and desensitization.

a. Keep each cat's food dishes at a distance where the cats can see each other but not react. If you can find this distance; very slowly move the dishes closer together.

b. Put the cats on leashes, and reward them when they don't react or when they react nicely to each other.

c. Use crates or gates so the animals can see but not injure each other.

d. Play games with or groom the cats so they learn that they can have good experiences when the other cat is present.

3. Correct and punish.

a. Place a bell on the cat's collar, and observe it with other animals.

b. Correct within the first 30 to 60 seconds of onset of behavior.

c. Use banishment.

4. Give rewards.

a. Reward if the cat responds to correction and will exhibit a better behavior. (if the cat looks away from the other cat, give it a treat.)

b. Reward when the cat is calm and quiet. Praise the cat for avoiding undesirable activities even if the cat is just sleeping.

c. Reward in small increments. Cats may not love each other but can learn to tolerate each other; reward even the smallest improvement.

d. Make sure all cats involved in the aggression get separate attention from the owner so the owner doesn't become currency.

5. Modify the environment.

a. Install barriers (e.g. doors and gates so animal is confined with the titter box).

b. Separate the problem cat from other cats in the household.

c. Clean and neutralize the odor,

d. Gradually reintroduce the animal to more of the home until litter box use is reliable.

TABLE 2

History Questionnaire for Cats with Elimination Disorders

1.How many litter boxes are available for the cat(s)? Enough so each cat has its own?

2.How many of the litter boxes are covered? Do the cats like the covered ones or avoid them?

3.What are the sizes of the boxes? Do the cats fit?

4. Where are the boxes? Is one location used more than the others?

5. How deep is the litter in each of the boxes? Does depth affect digging? Some cats like shallow litter; some like deep.

6. Are liners ever used? Some cats like these, but some hate them. It's all about feel and sensation.

7.If liners are used are they scented? Scent is often a problem.

8.List all types of litter used for each box.

9. Are any of the litters scented? Scent is often a problem.

10. Does the cat respond differently to any of the above styles of boxes or litters, sizes of boxes, or depths of litters? Use what the cat seems to prefer.

11.How frequently is the litter changed? Infrequent changings are a risk factor.

12. How frequently is the litter box washed and replaced? Infrequent washings and old boxes are risk factors.

13. Are deodorants used in the cleaning process? Some cats dislike deodorants.

14. How many cats actually share a litter box? If there is a use order, they may not actually be "sharing."

15. What does the cat do in the litter lox? Does it get in or stand outside? Does it dig inside or outside the box? These may hint that the cat does not like the litter.

16. Is the cat ever allowed outside? If so, what does it use for elimination there?

17. Does the animal eliminate in the presence of other animals or people, or is the elimination behavior secret? If the cat seems to prefer privacy, place the box appropriately.

18. Will the cat immediately use a freshly cleaned litter box? This suggests the need for very clean litter.

19. Has the cat ever had any change in whether or not it covers its feces or urine, and is that change associated with the presence or absence of any other situation or cat? Address these changes by accommodating the preferences.

20. Does the cat ever vocalize while it eliminates? Check for illness or pain.

21. Will the cat spray against the back of a covered litter box.? If so, you may be able to encourage the cat to use the box as an area to mark.

22. Does the animal ever use a shower or bathtub for elimination; if so, how frequently? This may indicate that the cat prefers open, well-drained substrates. Mimic this with its litter box

23. What other areas are used for elimination? (Get a complete list with locations and frequency of use.) Try to mimic locations and substrates.

24. Are the behaviors exhibited in the areas listed in question 23 different from those exhibited while the cat is in the litter box? Wherever the cat digs and seems to be comfortable; place the litter box.

Pharmacologic approaches

Environmental and behavior modification should be included in any treatment program that involves pharmacologic intervention. Furthermore, practitioners should remember that the Animal Medicinal Drug (Extra Label) Use Clarification Act of 1994 and the Animal Drug Availability Act of 1996 specify that before prescribing these medications, adequate physical (possibly including an electrocardiogram) and laboratory (a complete blood count and serum chemistry profile) examinations must be performed. Given that therapeutic and toxic ranges and side effects are seldom known for domestic animals, 6,7 veterinarians should be more compliant with guidelines than are physicians.

Clients who proceed with only drug treatment often maintain that the medication does not work. It is inappropriate to treat a behavior disorder pharmacologically without pursuing environmental and behavior modification as well as ruling out other disease processes before or along with drug therapy. Medications commonly used include benzodiazepines, tricyclic antidepressants (TCAs), and nonspecific anxiolytics. These more efficacious drugs have largely replaced progestin.

Pharmacologic intervention for preferences or aversions

The appropriate classes of drugs for treating aversions and preferences are TCAs and selective serotonin reuptake inhibitors (SSRis). These drugs are more specific in mode of action than the benzodiazepines, are not as often abused by people, do not induce physiologic tolerance, and have fewer potential side effects than drugs more commonly used in domestic animals (e.g. barbiturates, benzodiazepines, phenothiazine tranquilizers, progestins). TCAs are now also the drugs of choice for some cases of feline lower urinary tract disease and sterile cystitis, following the model for interstitial cystitis in people .8 It is important to remember that for most drugs that have been used for years, no toxicity data exist for ranges that are traditionally considered therapeutic, and no range of therapeutic levels has been validated. For most of these drugs, the side effects may be more profound and global since their mechanisms of action are global and nonspecific.

Amitriptyline, a TCA, can relieve the anxieties associated with specific stimuli, such as litters or litter boxes, but unlike the benzodiazepines does not interfere with learning. If a cat being treated with amitriptyline exhibits the relatively common side effect of emesis, the dose can be decreased, but the new dosage may not be sufficient to control the cat's anxiety. Alternatively, the cat could be treated with another TCA. For example, nortriptyline is the active intermediate metabolite of amitriptyline and does not have any active intermediate metabolites of its own. Side effects may be reduced, while efficacy is maintained.

If a cat cannot tolerate amitriptyline or nortriptyline, it may respond to buspirone as a therapy for preferences or aversions associated with the litter box, as evidenced in one study .9 In many cases, it is impossible to withdraw amitriptyline 7 or buspirone 9 and have the cats maintain appropriate litter box habits. This suggests that the cats have underlying, ongoing, endogenous anxiety about some condition associated with the box.

Cats have been successfully weaned from medication for litter box aversions or preferences when the clients aggressively manipulated the behavioral and physical environment. Cats are maintained on medication until at least three to four weeks have passed in which no inappropriate elimination has occurred. Since these medications take one to five weeks to modulate neurotransmitter receptor function, this means treating the cat for four to nine weeks. Cats can then be carefully weaned from the medication by decreasing the dose by half on a weekly basis. The pharmacokinetics of most of these drugs suggests that the minimum effective maintenance dose would be indicated by relapse. If clients abruptly discontinue medications, it is unclear to what extent the cats experience a rebound phenomenon associated with increased anxiety due to the sudden withdrawal of the antianxiety agent.

Benzodiazepines should not be used in cases involving either an aversion or a preference. Diazepam, the most frequently used benzodiazepine in cats, is a nonspecific antianxiety agent that has global gamma-aminobutyric acid (GABA) enhancement effects. Unfortunately, appropriate behaviors can also be inhibited when cats are treated with this drug. If the cat truly dislikes the litter but is also repulsed by a nonlitter substrate, the cat may actually be using the litter box more frequently than it wants to. This is classically seen in cats that are balancing on the edge of litter boxes but do not want to touch their feet to the substrate. Treating such a cat with a benzodiazepine may cause a global release of innate inhibition. In such a situation, it is not unusual to see the unwanted elimination behavior worsen. If you are not sure of the diagnosis and choose to use a benzodiazepine, the response can be diagnostic, but this approach is risky.

TABLE 3

Steps in Treating Feline Elimination Disorders

1. Rule out any potential underlying medical cause or other debilitating disease.

2. All affected areas and layers must be cleaned with an odor eliminator.

3. After cleaning, cover affected areas with heavy plastic to change the tactile sensation for the cat and prevent penetration in the event of further elimination.

4. Encourage the client to get multiple litter boxes, generally one more than there are cats, unless there are more than five cats; large numbers of cats may render the stimulus to eliminate inappropriately too strong. These litter boxes should be plated in a variety of locations and be offered in a variety of styles (open, covered, deep, shallow, big, small).

5. Litter should be scooped every day, and most litters (except clumping litters) should be dumped every other day. Many cats differ in their preference for litter depth. Boxes should be washed weekly. Older boxes may be so permeated with scent that they should be discarded.

6. A variety of litters should be offered to the cat in a variety of boxes. If the cat is using soft substances consider softer litters. If the problem involves a location preference or aversion, then a litter box with a litter the cat likes can be placed in the area. After one or two weeks the box can be slowly (one to two inches a day) moved to a more appropriate area. The client should watch for relapses or elimination in new spots.

7. Counterconditioning can work for some disorders involving locations. Food dishes can be placed in the affected areas. Rearrange the furniture or move a large plant so that the cat's favorite spot is covered. Because a scat mat doesn't change the perception of the regional environment, cats are likely to eliminate right next to the mat but not on it. This also applies to a vinyl carpet runner placed upside down so the points are up.

8. Cats are not trained to litter boxes; this is a behavior that develops in kittens in the absence of human intervention. Accordingly, we cannot train a cat with an elimination problem to use a litter box. However, cats can be encouraged to make positive associations with the box. The owner can take the cat to the litter box frequently and wait with it, praising it whenever it uses the box.

9. If the cat is seen squatting outside the box, startling and correction will work if the cat is startled in the first 30 to 60 seconds of the onset of the behavior (that includes circling, facial expressions, and digging) and if the scare is sufficient to make the cat abort the behavior and leave. Foghorns, water pistols, compressed air canisters, whistles, and tins of coins work with some cats. Physical punishment, including rubbing the cat's nose in the soiled area, is useless after the event.

10. Some cats may first need to be confined to a restricted area. Their access to the rest of the house can be expanded once they are using litter appropriately in the confined area. They should be watched closely as their access is slowly expanded.

Pharmacologic intervention for spraying and nonspraying marking

Most spraying and nonspraying marking is best treated by addressing problems in the social environment. Environmental behavior, and pharmacologic modification are generally all required. Treating the behavioral and physical environments alone will not be sufficient to stop the spraying unless the spraying has only recently started and is not yet habitual. In these cases in which spraying has been occasional or has just started and the client is able to identify what precipitated the spraying, modifying the physical and behavioral environments alone may be effective. If such an approach does not work within the first week, drug therapy must be initiated as quickly as possible. This is because, as discussed previously, olfactory cues are extremely important to cats, and every time a cat sprays, it is reinforcing an olfactory cue. Also, cats learn from these behaviors, and ignoring the problem could promote further social havoc.

The primary drugs used to treat feline spraying and nonspraying marking include TCAs such as amitriptyline, nortriptyline, and clomipramine; benzodiazepines such as diazepam; and nonspecific anxiolytics such as buspirone. There are no good data on whether other nonspecific antianxiety agents such as fluoxetine, paroxetine (Paxil°SmithKline Beecham), and sertraline (Zoloft®-Pfizer) are efficacious treatments, but based on their performance in other canine and feline behavior disorders10 it would not be surprising if these drugs were effective in treating some feline elimination disorders. The drug of choice has traditionally been diazepam. For more than a decade, diazepam has been used with varying degrees of success to treat spraying.

How buspirone and diazepam work

All spraying or nonspraying marking is not due to the same underlying cause, so no one drug works for all cats that exhibit this behavior. Spraying can be a nonspecific sign and a nonspecific diagnosis. Different cats may be experiencing different social and neurochemical stimuli for spraying. Because of this, learning as much as possible about the behaviors of the cats involved is a critical part of choosing the best drug for that cat. However, figuring out feline social interactions can be difficult and frustrating. Understanding social involvement may be the key to prescribing the appropriate drug, but a failed response can also provide critical information. This illustrates the importance of obtaining an excellent behavioral history, in which you can find out why the cat did not respond to the chosen drug.

It is appropriate to consider the modes of action of both buspirone and diazepam for cats with nonspraying marking or spraying disorders. All benzodiazepines have global, anxiolytic effects. They amplify the effects of the inhibitory neurotransmitter GABA, and they may help encourage social interactions, because they inhibit anxiety.11-13 Owners may report that some cats become excessively friendly while receiving benzodiazepines. This social effect may be the reason cats stop spraying in successful cases. In such cases, the spraying is secondary to or symptomatic of the social conflict.

Benzodiazepines cause patients to be less reactive to their surroundings and less responsive to provocative stimuli. This appears to be the main reason they are used to treat feline spraying.

The benzodiazepines have mood elevation effects because of their effects on the inhibitory neurotransmitter, not because they elevate brain chemicals associated with upbeat moods, such as serotonin.13 Such subtleties may play a role in treating complex social phenomena such as spraying. Diazepam has a notoriously short half-life in cats, so it is likely that the intermediate metabolite, desmethyldiazepam, is acting as the efficacious, therapeutic compound. When used correctly, diazepam controls spraying in 75 to 90% of all cats.2 3

Cats may stagger a bit and have impaired depth perception for a few days. These effects are probably attributable to the pharmacokinetics of desmethyldiazepam. As steady-state levels are reached within three to five days the staggering should resolve spontaneously.14 If the incoordination does not pass within four to seven days, the cat's dose may be too high. In situations involving spraying, decreasing the dose stops the incoordination but does not hamper the therapeutic effects. If the cat never staggers or acts uncoordinated, it is possible that it is not receiving a high enough dose of the intermediate metabolite. Some cats may require treatment for a few weeks, some seasonally, some forever. For any drug, the lowest effective dose should be used. Some cats that do not respond to diazepam require a benzodiazepine with a longer half-life.

Some cats treated with benzodiazepines never act uncoordinated but progress immediately to being drugged. Obviously, benzodiazepines are not the appropriate treatment for these cats. Hepatotoxicity has been reported in cats treated with both generic and brand-name diazepam.15,l6 Such reports appear to be rare and idiosyncratic and implicate a role for desmethyldiazepam. There is an over-representation of obese patients. Few of the animals that were treated and died had been subjected to premedication laboratory evaluation (which might have revealed liver enzyme abnormalities).15-16 Too little information is available to determine diazepam's specific role in these reactions because of the absence of premedication laboratory evaluation.

When diazepam treatment is stopped, relapses are common. Subsequent treatment with diazepam may require a higher dose than previously used to treat the spraying. Occasionally, the cat is refractory. There are no data from a sufficiently large sample on the extent to which either cats become refractory or subsequent dosing requires an increase of dose. Such a response is likely to be due to physiologic dependence. 17

Psychologic addiction does not appear to be a problem in animals, perhaps because they cannot selfmedicate. Benzodiazepines can be abused by people, and clients should be warned of this. Because many animals are maintained on medication for spraying for a long time, it is inadvisable for you to dispense a large amount of any benzodiazepine at one time. It is preferable to repeatedly renew a prescription once a month or every other month. This also gives you the opportunity to get updates on the cats' behavioral condition.

Buspirone is a nonspecific anxiolytic that appears to act as a partial serotonin agonist, both presynaptically and postsynaptically. 18-20 it has been suggested that buspirone's primary effect may even be as a dopamine receptor agonist.20 Any effects on serotonin or dopamine could render the patient less anxious about perceived social threats while increasing its capability to interact socially. The extent to which spraying is a signal or an aggressive act in such circumstances would influence the extent to which the drug decreased the behavior. Aggression (and spraying can be an aggressive act 14,21) is behaviorally complex; it is not surprising that different pharmacologic compounds generate a variety of therapeutic responses. You should try to explore the efficacy of all relative compounds that may work for your patient.

Choosing between buspirone and diazepam

It has become popular to use buspirone instead of benzodiazepines to treat spraying.9 A critical review of data from two studies indicates that, in general, buspirone is no more successful than diazepam overall and is more expensive, so consider cost before recommending a client invest in the typical six to 12 months of buspirone therapy.3 9

One investigator presented data that indicated that 43% (10 of 23) of cats treated with diazepam for spraying ceased spraying totally.3 Seventy-four percent of the cats (17 of 23) that were treated for spraying with diazepam experienced a 75% or better reduction in spraying. These data are slightly more favorable than those presented in another study that indicated that 55% (11 of 20) experienced a reduction in spraying .2 Each study relied on a very small sample size (23 and 20, respectively). Treatment with buspirone resulted in a 75% or better reduction in spraying in 52% (32 of 62) of cats in one study.9 Twentyone of the 32 cats that responded stopped spraying completely. When the data from this buspirone study and one of the diazepam studies are compared,3,9 they are not significantly different with regard to the number of patients experiencing at least a 75% reduction in spraying (P >0.05). The data presented in the buspirone study are also not significantly different from the previous data reported for diazepam] when the number of patients ceasing to spray are compared (P >0.05). Accordingly, buspirone is no more effective than diazepam overall in treating feline spraying or in affecting the proportion of the population that ceases spraying altogether.

More work is needed in these areas, including larger sample sizes. An expanded study, particularly one that notes behavior aspects of animals that responded and those that did not respond, could identify the animals most likely to respond to different medications. Unfortunately, the role of the social environment is not explored or discussed in either of these studies. In multicat households, 58% (32 of 55) of cats responded to buspirone while none from single-cat households did.9 This strongly suggests that the social environment is critical in determining the underlying cause of spraying and in suggesting a drug that will help. Various researchers have noted that buspirone-responsive cats may become more assertive to other cats or more willing to interact in general.9,10 These instances suggest that data about social changes may provide clues about how both drugs act and why spraying occurred in the first place. Evaluating and intervening in the social environment is important when treating complex problems such as spraying.

Relapse rates for animals that spray are notoriously high. Again, this may in part be due to the lack of appreciation of the interacting social environment. Two studies differ dramatically with regard to relapse rates for cats treated for spraying with diazepam. One study reports that 91% (10 of 11) resumed spraying when diazepam was discontinued,9 while another reports that 76% (13 of 17) reverted at some time.3 For buspirone, the relapse rate was 53% (17of 32) when the drug was withdrawn after eight weeks. These results (13 of 17 vs. 17 of 32) are not significantly different (P>0.05).

The investigators do not note the time frame over which the withdrawal was done nor do they note the accompanying dosage schedule. Time frame and dosage schedules are important because the data discussed refer to an eight-week time period, so the relapse rate for buspirone might be higher if the time period was longer. This is especially true since it can take from two to four weeks for blood levels of buspirone to reach therapeutic levels in people and dogs.3,19 Clearance time may also be prolonged in such cases, making assessments for relapse rates that are computed for times close to drug cessation unreliable.

The relative effects of diazepam and buspirone must be considered when choosing which medication is best for your patient. Diazepam works well in situations in which aggression and the resultant elimination disorder are secondary to social anxiety. Accordingly, diazepam works well in 1) intercat aggression involving passive or covert aggression with spraying or nonspraying marking; 2) intercat aggression involving active or overt aggression with spraying and nonspraying marking, particularly if it is in response to a perceived change in the environment 9; 3) location aversions secondary to fear and anxiety associated with aggression; 4) situations wherein a quick response is needed (and both drugs are equally effective), since within a week the owner should be able to detect some change in the animal's behavior; 5) situations in which finances are a concern; and 6) situations wherein diazepam has worked in the past, although a higher dosage may be needed for subsequent treatments.

Some animals may be refractory to the drug. Regardless, if the cat is experiencing a relapse due to the same social stimuli that provoked it before and diazepam worked then, it may work the next time.

Buspirone works well in situations in which aggression is the primary problem, cases involving very confident cats, and cases in which cats are unable to make themselves sufficiently assertive within the social system. Buspirone facilitates social interactions and alterations in hierarchical relationships. Buspirone is useful in 1) intercat aggression involving active aggression with spraying or nonspraying marking; 2) status-related aggression associated with spraying (in this case it facilitates more appropriate social hierarchical relationships and diminishes the status of outright aggression); 3) situations in which a longer half-life is required and expense is not an issue; 4) cases in which the cat is expected to be maintained on the drug, because physiologic tolerance occurs with diazepam and buspirone cannot be abused by people; 5) cases in which TCAs and benzodiazepines have failed or have made the cat ill; and 6) cases in which aggression is a serious concern.

Buspirone has special implications in these latter situations. If two cats are involved in an aggressive event and one has become absolutely terrified, giving diazepam to the terrified cat may help impede the cat's shortterm memory of horrific events and make the cat friendlier. Buspirone, given to the aggressor, may then facili .fate appropriate social interaction between the two because it relieves the anxiety associated with aggression. This treatment is appropriate if the aggressor has maintained its anxiety and aggression despite all information received from the victim that the latter

poses no threat. In other words, the aggressor is behaving inappropriately-the victim responded in an acceptable way. The aggressor may also be inhibiting some of its aggression because it has learned that this behavior is inappropriate for other reasons (e.g. the owners have punished the cat). In this case, diazepam is not an appropriate drug for the aggressor since it can relieve inhibitions, including those involving aggression. This is the one situation in which the confident, actively aggressive cat that is not demonstrating the full extent of its aggressive propensities may do better being treated with buspirone than with diazepam.

Diazepam may be appropriate for a cat that is anxious about its relative status and is overtly aggressive, regardless of the other cat's response to this aggression. The drug renders such individuals friendlier and relieves anxieties so that these cats can function more appropriately in the social hierarchy. Clomipramine may also work well in these cases. The recipient of the aggression in this situation may do well on buspirone, since it may make the recipient more assertive. It is important to emphasize that the drugs are being used not only to treat underlying anxiety but to facilitate concomitant behavior modification (Table 1).

Finally, keep this in mind when treating an aggressive cat whose victim is withdrawn and terrified. A confident bully should not be treated with buspirone if the drug makes the cat more assertive. In this case, the bully should be treated with an agent that renders it friendlier (diazepam), while the recipient is treated with an agent that relieves its anxiety and facilitates its reintroduction to the social system. Because of its tendency to encourage assertion, buspirone may be preferable for the recipient, but diazepam and clomipramine may work equally well.

Other options

The new treatment involving a synthetic analogue of feline cheek glands (FeliwayTM-Abbott Laboratories) may show some promise for spraying that has just started and is related to the introduction of a new person or animal or to disruptions in the colony scent. No doubleblind studies have been conducted, and the need for such studies is more critical in this situation than in those involving some oral medications, because of the manner in which the pheromone is applied and the need for clients to be cautious in their interpretations.

The only rigorous study to date that has looked at the use of Feliway for the treatment of spraying found that in many cases there was a statistically significant reduction in spraying, but few to no cats stopped spraying altogether (Unpublished data: D. Frank et al, 1997). That's to be expected if the problem stems from anxiety and not from the actual pheromonal environment. In some cases the concomitant use of pheromonal agents and antianxiety medications may

produce a quicker resolution than would be produced by either alone. The neurochemical mechanism by which such pheromonal sprays may work is unknown, but it might be worthwhile, given the pattern of findings in the above study, to explore the extent to which pheromones can act as aerosolizable anxiolytics.

The primary drugs of choice for treating feline spraying are diazepam and buspirone. In some cases involving specific anxiety-producing stimuli, TCAs and SSRls can be useful. For nonspraying marking the TCA amitriptyline may be useful, particularly if there is a location or substrate aversion. It does not matter whether the substrate or location aversion is primary or secondary. Clomipramine has only recently been used in the United States to treat spraying, although it has been used successfully in experimental situations in Switzerland for a number of years. 22 Clomipramine appears to be equally efficacious in situations involving one or multiple cats and in situations involving anxious cats that are refractory to other medications. There is no information about its efficacy in cases involving marking associated with sexual advertisement.